Benzoyl peroxide (“BPO”) has long been used for treatment of dermatological lesions and is also known to be an effective anti-microbial and anti-keratolytic agent useful, for example, in the treatment of acne. Benzoyl peroxide is a non-toxic, colorless, odorless, and tasteless crystalline solid with a molecular weight of 242.22 and a melting point of between about 103° and 106° C. Pure (98% active) benzoyl peroxide crystals are commercially available but are considered explosive. Hence special precautions must be taken when handling pure BPO during preparation, transportation, and storage. BPO is also commercially available as a 75% crystalline solid with 25% water and is available from a number of suppliers, primarily in the plastics industry.
Conventional BPO crystalline powder requires milling for several hours in water through high shear mills to prepare a paste having crystals that are sufficiently fine to be of acceptable texture for preparing products for topical use. Such crystals are typically average at least 20 microns. These BPO crystals may be used to treat dermatological lesions. However, the BPO crystals contacting the skin may have adverse irritative effects. The BPO Monograph finalized Mar. 4, 2010 (75 FR 9768) cites 47 FR 12430 at 12444 as disclosing that BPO “is known to be a skin irritant and sensitizer in humans.” These adverse effects appear to result, at least in part, from excessive concentrations of BPO at skin areas in contact with BPO particles. Methods for avoiding such adverse effects, while still effectively utilizing BPO therapeutically, have been long-sought.
Certain prior attempts to create stable, pharmaceutically effective and dermatologically non-irritative BPO preparations have involved the production of minute BPO crystals. U.S. Pat. No. 4,401,835, issued to Tarasoy, describes a method of preparing BPO crystals that are less than ten microns in size. The method includes the steps of: (1) preparing a first solution comprising BPO and a precipitate promoting material; (2) adding the first solution to a second solution that causes the BPO to precipitate as a fine crystalline dispersion; and (3) recovering the BPO crystals which may be washed or used directly. The precipitate promoting material is a solvent for BPO that is able to produce a solution containing up to about 15% by weight BPO. In one case the solvent is dimethyl ether of 1,4:3,6-dianhydrosorbitol (dimethyl isosorbide) or tetrahydrothiophene-1,1-dioxide. The second solution is an aqueous solution of a non-toxic dispersant which is non-reactive with BPO. This dispersant is a cellulose derivative or a surfactant (non-ionic or anionic). However, solvents used to prepare the BPO crystals may have solvent residues that also irritate the skin. Hence it is desirable to provide a solvent-free, irritation-free, BPO formulation.